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Arteriovenous fistula (AVF) dysfunction is a common complication in patients undergoing maintenance hemodialysis (MHD). Elevated serum levels of fibroblast growth factor 21 (FGF21) are associated with atherosclerosis and cardiovascular mortality. However, its association with vascular access outcomes remains elusive. The present study evaluated the relationship of serum FGF21 levels with AVF dysfunction and all-cause mortality in patients undergoing MHD. We included patients undergoing MHD using AVF from January 2018 to December 2019. FGF21 concentration was detected using enzyme-linked immunosorbent assay. Patients were followed up to record two clinical outcomes, AVF functional patency loss and all-cause mortality. The follow-up period ended on April 30, 2022. Among 147 patients, the mean age was 58.49 ± 14.41 years, and the median serum level of FGF21 was 150.15 (70.57–318.01) pg/mL. During the median follow-up period of 40.83 months, the serum level of FGF21 was an independent risk factor for AVF functional patency loss (per 1 pg/mL increase, HR 1.002 [95% CI: 1.001–1.003, p = 0.003]). Patients with higher serum levels of FGF21 were more likely to suffer from all-cause mortality (per 1 pg/mL increase, HR 1.002 [95% CI: 1.000–1.003, p = 0.014]). The optimal cutoffs for FGF21 to predict AVF functional patency loss and all-cause mortality in patients undergoing MHD were 149.98 pg/mL and 146.43 pg/mL, with AUCs of 0.701 (95% CI: 0.606–0.796, p < 0.001) and 0.677 (95% CI: 0.595–0.752, p = 0.002), respectively. Serum FGF21 levels were an independent risk factor and predictor for AVF functional patency loss and all-cause mortality in patients undergoing MHD. [ABSTRACT FROM AUTHOR]

Illicium verum Hook. f. is a globally significant spice, which is recognized in China as a food-medicine homolog and extensively utilized across the pharmaceutical, food, and spice industries. China boasts the world's leading resources of I. verum, yet its comprehensive utilization remains relatively underexplored. Through a resource survey of I. verum and the application of bibliometric visualization using CiteSpace, this study analyzed 324 papers published in the Web of Science Core Collection (WOSCC) from 1962 to 2023 and 353 core documents from China's three major databases (CNKI, Wanfang Database, and VIP Database). I. verum from Guangxi province towards various southern provinces in China, with autumn fruits exhibited superior quality and market value over their spring fruits. Literature in WOSCC emerged earlier, with a research emphasis on food science technology and pharmacology pharmacy domains. WOSCC research on I. verum could be divided into two phases: an embryonic period (1962–2001) and a growth period (2002–2023), showing an overall upward trend in publication. The three major Chinese databases contain a larger number of publications, with a focus on the food sector, which could be categorized into three stages: an embryonic period (1990–1999), a growth period (2000–2010), and a stable period (2011–2023), with an overall downward trend in publication. Both Chinese and international research hotspots converge on the medical applications of I. verum, with antioxidant bioactivity research emerging as a prevailing trend. This study delineated the resource distribution of I. verum across China and identified the research hotspots and trends both in China and internationally. The findings are beneficial for guiding researchers in swiftly establishing their research focus and furnishing decision-makers with a comprehensive reference for industry information. [ABSTRACT FROM AUTHOR]

Background: Congenital ectopia lentis (EL) refers to the congenital dysplasia or weakness of the lens suspensory ligament, resulting in an abnormal position of the crystalline lens, which can appear as isolated EL or as an ocular manifestation of a syndrome, such as the Marfan syndrome. The fibrillin‐1 protein encoded by the FBN1 gene is an essential component of the lens zonules. Mutations in FBN1 are the leading causes of congenital EL and Marfan syndrome. Owing to the complexity and individual heterogeneity of FBN1 gene mutations, the correlation between FBN1 mutation characteristics and various clinical phenotypes remains unclear. Methods: This study describes the clinical characteristics and identifies possible causative genes in eight families with Marfan syndrome or isolated EL using Sanger and whole‐exome sequencing. Results: Eight FBN1 mutations were identified in these families, of which three (c.5065G > C, c.1600 T > A, and c.2210G > C) are reported for the first time. Based on in silico analyses, we hypothesized that these mutations may be pathogenic by affecting the fibrillin‐1 protein structure and function. Conclusion: These findings expand the number of known mutations involved in EL and provide a reference for the research on their genotype and phenotype associations. [ABSTRACT FROM AUTHOR]

Bletilla spp. Rchb. F. is a traditional Chinese medicinal material. In this study, Bletilla striata (Thunb. ex A. Murray) Rchb F, Bletilla formosana (Hayata) Schltr, and Bletilla ochracea Schltr were collected to analyze the genetic diversity of 16 materials using specific site-amplified fragment sequencing (SLAF-seq) and fluorescence in situ hybridization (FISH). The results showed that the phylogenetic tree of the single-nucleotide polymorphism (SNP) data rendering system was correlated with the shape and geographical distribution of the material. The results of the population structural analysis showed that all the materials containing yellow labellum came from the same ancestor. The results of the principal component analysis were able to preliminarily judge the genetic distance and provided a reference for the selection of hybrid parents. The FISH analysis showed that the chromosomes of B. striata were 2n = 32 and the chromosomes of the B. striata (safflower) mutant were 2n = 34 and the chromosomes of B. ochracea and B. formosana were 2n = 34–36. The (AG3T3)3 non-terminal signal was different from the 5S rDNA signal. These results revealed that the 16 materials had rich genetic diversity, which can provide molecular and cytogenetic data for the study of the genus and its relatives and serve as a reference for the breeding of new genus varieties and improve breeding efficiency and cost. [ABSTRACT FROM AUTHOR]

The tropical plant Plumbago auriculata can tolerate subzero temperatures without induction of apoptosis after cold acclimation in autumn, making it more cold tolerant than conventional tropical plants. In this study, we found that low temperatures significantly affected the photosynthetic system of P. auriculata. Using transcriptome sequencing, PaDREB1A was identified as a key transcription factor involved in the response to cold stress in P. auriculata. This transcription factor may be regulated by upstream JA signaling and regulates downstream ERD4 and ERD7 expression to resist cold stress. Overexpression of PaDREB1A significantly enhanced freezing resistance, protected the photosynthetic system, and enhanced the ROS scavenging mechanism under cold stress in Arabidopsis thaliana. Additionally, PaDREB1A significantly enhanced the expression of CORs and CAT1 in A. thaliana , which further activated the downstream pathway to enhance plant cold tolerance. This study explored the possible different regulatory modes of CBFs in tropical plants and can serve as an important reference for the introduction of tropical plants to low-temperature regions. [ABSTRACT FROM AUTHOR]

Abstract Background CD8+ regulatory T cells (Treg) have been considered to be involved in a model of ocular-induced tolerance, known as anterior chamber-associated immune deviation (ACAID). The phenotype and characteristics of CD8+Treg in ACAID remain only poorly understood. Recent studies have reported that the CD94-Qa-1 system is implicated in the induction of ACAID CD8+Treg, but the functions and characteristics of CD8+CD94+T cells remain unclear. Results Both mRNA and protein of CD94 and NKG2A were markedly up-regulated on splenic CD8+T cells of ACAID mice compared with controls. Flow cytometric analysis showed that very few CD8+CD94+T cells express granzyme B, perforin and Foxp3. CD8+CD94+T cells, but not CD8+CD94-T cells, magnetically isolated from the spleens of ACAID mice, produced large amounts of TGF-beta1 and exhibited suppressive activity in vitro. Neutralization of TGF-beta1 caused reversal of suppression mediated by CD8+CD94+T cells. Conclusion CD8+CD94+T cells from ACAID mice exhibited suppressive activity in association with enhanced expression of TGF-beta1, suggesting that CD8+Treg are mainly distributed in CD94+T cell subpopulations.

The first complete chloroplast genome (cpDNA) sequence of Lophatherum gracile Brongn. was determined from Illumina HiSeq pair-end sequencing data in this study. The cpDNA is 140,595 bp in length, contains a large single-copy region (LSC) of 82,447 bp, and a small single-copy region (SSC) of 12,626 bp, which were separated by a pair of inverted repeats (IR) regions of 22,761 bp. The genome contains 130 genes, including 83 protein-coding genes, eight ribosomal RNA genes, and 39 transfer RNA genes. The further phylogenomic analysis showed that L. gracile and Zeugites pittieri clustered in a clade in Poaceae family. [ABSTRACT FROM AUTHOR]

Introduction: Interleukin-18 (IL-18), a pro-inflammatory cytokine belonging to the IL-1 Family, is a key mediator ofautoinflammatory diseases associated with the development of macrophage activation syndrome (MAS).High levels of IL-18 correlate with MAS and COVID-19 severity and mortality, particularly in COVID-19patients with MAS. As an inflammation inducer, IL-18 binds its receptor IL-1 Receptor 5 (IL-1R5), leadingto the recruitment of the co-receptor, IL-1 Receptor 7 (IL-1R7). This heterotrimeric complex subsequentlyinitiates downstream signaling, resulting in local and systemic inflammation., Methods: We reported earlier the development of a novel humanized monoclonal anti-human IL-1R7 antibody whichspecifically blocks the activity of human IL-18 and its inflammatory signaling in human cell and wholeblood cultures. In the current study, we further explored the strategy of blocking IL-1R7 inhyperinflammation in vivo using animal models., Results: We first identified an anti-mouse IL-1R7 antibody that significantly suppressed mouse IL-18 andlipopolysaccharide (LPS)-induced IFNg production in mouse splenocyte and peritoneal cell cultures. Whenapplied in vivo, the antibody reduced Propionibacterium acnes and LPS-induced liver injury and protectedmice from tissue and systemic hyperinflammation. Importantly, anti-IL-1R7 significantly inhibited plasma,liver cell and spleen cell IFNg production. Also, anti-IL-1R7 downregulated plasma TNFa, IL-6, IL-1b,MIP-2 production and the production of the liver enzyme ALT. In parallel, anti-IL-1R7 suppressed LPSinducedinflammatory cell infiltration in lungs and inhibited the subsequent IFNg production andinflammation in mice when assessed using an acute lung injury model., Discussion: Altogether, our data suggest that blocking IL-1R7 represents a potential therapeutic strategy to specificallymodulate IL-18-mediated hyperinflammation, warranting further investigation of its clinical application intreating IL-18-mediated diseases, including MAS and COVID-19., Competing Interests: KB was employed by MAB Discovery GmbH, Germany. UP and DP were employed by MAB Discovery GmbH and IcanoMAB GmbH, Germany. SF is the CEO of MAB Discovery GmbH and IcanoMAB GmbH. JF received consulting fees from MAB Discovery GmbH. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Jiang, Lunding, Webber, Beckmann, Azam, Falkesgaard Højen, Amo-Aparicio, Dinarello, Nguyen, Pessara, Parera, Orlicky, Fischer, Wegmann, Dinarello and Li.)

Bletilla striata is an endangered traditional medicinal herb in China. In May 2020, the emergence of white root rot severely impacted the quality and yield of B. striata , affecting about 5% of the plants at plant nurseries of the Chengdu Academy of Agricultural and Forestry Sciences. Through a series of experiments and evaluations, the pathogen was identified as Fusarium solani . This is the first report of B. striata white root rot caused by F. solani in Sichuan, China. To better understand this disease and provide data support for its control, a combination of morphological, molecular characterisation and pathogenicity determination was used in this study for assessment. Meanwhile, the effects of different carbon and nitrogen sources, culture medium, temperature, photoperiod and pH on mycelial growth and spore production of F. solani were investigated. In addition, effective fungicides were screened and the concentration ratios of fungicides were optimized using response surface methodology (RSM). The experimental results showed that sucrose was the optimum carbon source for the pathogen, and the optimum temperature and pH were 25°C and pH 7, respectively, while light did no significant effect. Effective fungicides were screened, among which difenoconazole showed the strongest inhibition with EC 50 of 142.773 µg/mL. The optimum fungicide concentration scheme (difenoconazole, pyraclostrobin, and thiophanate-methyl at 395.42, 781.03, and 561.11 µg/mL, respectively) was obtained using response surface methodology (RSM) to improve the inhibition rate of 92.24 ± 0.34%. This study provides basic data for the pathogen characterization of B. striata white root rot and its potential fungicides in Sichuan, China. In addition, the optimal fungicide concentration ratios were obtained through response surface methodology (RSM) optimization, which significantly enhanced the fungicidal effect and provided a scientific basis for the future control of B. striata white root rot., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liang, Jiang, Liu, Wang, Liu, Hu, Tan, Chen, Xu, Xu, Jiang, Liu and Yang.)

Under salt stress, recretohalophyte Plumbago auriculata tetraploids enhance salt tolerance by increasing selective secretion of Na + compared with that in diploids, although the mechanism is unclear. Using non-invasive micro-test technology, the effect of salt gland Ca 2+ content on Na + and K + secretion were investigated in diploid and tetraploid P. auriculata under salt stress. Salt gland Ca 2+ content and secretion rates of Na + and K + were higher in tetraploids than in diploids under salt stress. Addition of exogenous Ca 2+ increased the Ca 2+ content of the salt gland in diploids and is accompanied by an increase in the rate of Na + and K + secretion. With addition of a Ca 2+ channel inhibitor, diploid salt glands retained large amounts of Ca 2+ , leading to higher Ca 2+ content and Na + secretion rate than those of tetraploids. Inhibiting H 2 O 2 generation and H + -ATPase activity altered Na + and K + secretion rates in diploids and tetraploids under salt stress, indicating involvement in regulating Na + and K + secretion. Our results indicate that the increased Na + secretion rate of salt gland in tetraploids under salt stress was associated with elevated Ca 2+ content in salt gland., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Duan, Jiang, Lei, Ouyang, Liu, Zhao, Li, Yang, Li, Yi and Gao.)

Unchecked inflammation can result in severe diseases with high mortality, such as macrophage activation syndrome (MAS). MAS and associated cytokine storms have been observed in COVID-19 patients exhibiting systemic hyperinflammation. Interleukin-18 (IL-18), a proinflammatory cytokine belonging to the IL-1 family, is elevated in both MAS and COVID-19 patients, and its level is known to correlate with the severity of COVID-19 symptoms. IL-18 binds its specific receptor IL-1 receptor 5 (IL-1R5, also known as IL-18 receptor alpha chain), leading to the recruitment of the coreceptor, IL-1 receptor 7 (IL-1R7, also known as IL-18 receptor beta chain). This heterotrimeric complex then initiates downstream signaling, resulting in systemic and local inflammation. Here, we developed a novel humanized monoclonal anti-IL-1R7 antibody to specifically block the activity of IL-18 and its inflammatory signaling. We characterized the function of this antibody in human cell lines, in freshly obtained peripheral blood mononuclear cells (PBMCs) and in human whole blood cultures. We found that the anti-IL-1R7 antibody significantly suppressed IL-18-mediated NFκB activation, reduced IL-18-stimulated IFNγ and IL-6 production in human cell lines, and reduced IL-18-induced IFNγ, IL-6, and TNFα production in PBMCs. Moreover, the anti-IL-1R7 antibody significantly inhibited LPS- and Candida albicans-induced IFNγ production in PBMCs, as well as LPS-induced IFNγ production in whole blood cultures. Our data suggest that blocking IL-1R7 could represent a potential therapeutic strategy to specifically modulate IL-18 signaling and may warrant further investigation into its clinical potential for treating IL-18-mediated diseases, including MAS and COVID-19., Competing Interests: Conflict of interest K. B. and U. P. were employed by MAB Discovery GmbH, Neuried, Germany. S. F. is the CEO of MAB Discovery GmbH. J. F. H. has received consulting fees from MAB Discovery GmbH. Other authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

The first complete chloroplast genome (cpDNA) sequence of Lophatherum gracile Brongn. was determined from Illumina HiSeq pair-end sequencing data in this study. The cpDNA is 140,595 bp in length, contains a large single-copy region (LSC) of 82,447 bp, and a small single-copy region (SSC) of 12,626 bp, which were separated by a pair of inverted repeats (IR) regions of 22,761 bp. The genome contains 130 genes, including 83 protein-coding genes, eight ribosomal RNA genes, and 39 transfer RNA genes. The further phylogenomic analysis showed that L. gracile and Zeugites pittieri clustered in a clade in Poaceae family., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Patients with chronic kidney disease (CKD) often exhibit associated endothelial dysfunction and inflammation. Systemic inflammation may contribute to the endothelial dysfunction and accelerated thrombosis observed in CKD patients. In this study, we assessed the relationships among endothelial dysfunction, a disintegrin-like and metalloprotease with thrombospondin type 1 repeats 13 (ADAMTS13) activity and levels of inflammatory cytokines in CKD patients. CKD patients were classified into three groups: The chronic glomerulonephritis group (CGN; n=31), the idiopathic nephritic syndrome group (NS; n=32) and the lupus nephritis group (LN; n=41). We measured the plasma levels of tumor necrosis factor-α (TNF-α), von Willebrand factor (VWF) antigen (VWF:Ag) and ADAMTS13 activity using an ELISA-based method in CKD patients (n=104) and normal controls (n=32). The ratio of the VWF:Ag levels to ADAMTS13 activity was calculated. The VWF:Ag levels were significantly higher and the ADAMTS13 activities were significantly lower in the disease groups compared to the controls (P<0.01). ADAMTS13 activity was lower in the NS group compared to the CGN and LN groups (P<0.05). The TNF-α levels were higher in the CKD group compared to the control group (P<0.01). TNF-α was positively correlated with the VWF:Ag levels (r=0.242, P=0.013) and negatively correlated with the glomerular filtration rate (GFR) (r=-0.193, P=0.049). ADAMTS13 activity was negatively correlated with the cholesterol levels in CKD patients (r=-0.2, P= 0.042). TNF-α levels in CKD were positively correlated with the VWF:Ag levels and negatively correlated with GFR, which indicates that inflammation may be a major cause of endothelial dysfunction and an index of renal function. The VWF:Ag levels increased and ADAMTS13 activity decreased in CKD patients, which indicates that CKD leads to a prothrombotic state.

Purpose: To characterize the clinical features of a Chinese Uygur pedigree with primary open-angle glaucoma (POAG) and to identify mutations in two candidate genes, trabecular meshwork inducible glucocorticoid response (MYOC/TIGR) and human dioxin-inducible cytochrome P450 (CYP1B1)., Methods: Twenty one members from a Chinese Uygur family of four generations were included in the study. All participants underwent complete ophthalmologic examinations. Five were diagnosed as POAG, four as glaucoma suspects, and the rest were asymptomatic. Molecular genetic analysis was performed on all subjects included in the study. All exons of CYP1B1 and MYOC were amplified by polymerase chain reaction (PCR), sequenced and compared with a reference database. The variations detected were evaluated in available family members as well as 102 normal controls. Possible changes in structure and function of the protein induced by amino acid variance were predicted by bioinformatics analysis., Results: Elevated intraocular pressure and late-stage glaucomatous cupping of the optic disc were found in five patients of this family. A novel heterozygous missense mutation c.1151 A>G in exon 3 of MYOC was found in all five patients diagnosed as POAG and four glaucoma suspects, but not in the rest of the family members and 102 normal controls. This mutation caused an amino acid substitution of aspartic acid to glycine at position 384 (p. D384G) of the MYOC protein. This substitution may cause structural and functional changes of the protein based on bioinformatics analysis. No mutations were found in CYP1B1., Conclusions: Our study suggests that the novel mutation D384G of MYOC is likely responsible for the pathogenesis of POAG in this pedigree.

Background: CD8+ regulatory T cells (Treg) have been considered to be involved in a model of ocular-induced tolerance, known as anterior chamber-associated immune deviation (ACAID). The phenotype and characteristics of CD8+Treg in ACAID remain only poorly understood. Recent studies have reported that the CD94-Qa-1 system is implicated in the induction of ACAID CD8+Treg, but the functions and characteristics of CD8+CD94+T cells remain unclear., Results: Both mRNA and protein of CD94 and NKG2A were markedly up-regulated on splenic CD8+T cells of ACAID mice compared with controls. Flow cytometric analysis showed that very few CD8+CD94+T cells express granzyme B, perforin and Foxp3. CD8+CD94+T cells, but not CD8+CD94-T cells, magnetically isolated from the spleens of ACAID mice, produced large amounts of TGF-beta1 and exhibited suppressive activity in vitro. Neutralization of TGF-beta1 caused reversal of suppression mediated by CD8+CD94+T cells., Conclusion: CD8+CD94+T cells from ACAID mice exhibited suppressive activity in association with enhanced expression of TGF-beta1, suggesting that CD8+Treg are mainly distributed in CD94+T cell subpopulations.

Purpose: To examine the expression of Foxp3 on CD8+ T cells in the spleen during anterior chamber-associated immune deviation (ACAID)., Methods: Ovalbumin (OVA) was injected into the anterior chamber (AC) of C57BL/6 mice, and the delayed-type hypersensitivity (DTH) response was measured to evaluate the development of ACAID. The suppressive effect of CD8+ T cells in ACAID mice was determined by a local adoptive transfer (LAT) assay. Flow cytometry was used to assay the frequency of CD8+ Foxp3+ T cells from normal mice, ACAID mice, and control mice receiving an AC injection of PBS (PBS-AC-injected mice). These frequencies were also tested after polyclonal or specific antigen stimulation. The mRNA level of Foxp3 in CD8+ splenocytes from different groups with or without stimulation were determined by reverse transcription-polymerase chain reaction., Results: OVA injection into the AC induced ACAID, and CD8+ T cells from ACAID mice inhibited the ear-swelling response by OVA-primed responder cells in LAT assay. Flow cytometry analysis showed that the frequency of CD8+ Foxp3+ cells in splenocytes was upregulated in ACAID mice following polyclonal or specific antigen stimulation. Foxp3 mRNA was only detected in CD8+ T cells from ACAID mice after polyclonal stimulation., Conclusions: An upregulated Foxp3 expression in CD8+ T cells is associated with the development of ACAID, suggesting an involvement of CD8+ Foxp3+ T cells in this model of immune tolerance.